Steroid Hormone Receptors Flashcards
What does “not all ligands are steroids” mean?
Not all ligands are cholesterol derivatives
What ligands are cholesterol derivatives?
- cortisol
- estradiol
- testosterone
- aldosterone
What is the function of carrier proteins?
helps get signal molecule widespread throughout body
Most important carrier protein for cortisol?
transcortin
Most important carrier for thyroid hormone?
thyroxine-binding-globulin
Members of the steroid hormone receptor superfamily all contain what structures?
- transcription-activating domain
- DNA binding domain
- hormone-binding domain
Common signaling mechanism for steroid hormone receptors
- DNA-binding site is hidden by an inhibitory protein complex.
- The steroid hormone enters and binds to its receptor
- The inhibitory protein releases and the DNA-binding site is now exposed
Examples of steroid hormone receptors in the cytosol
- glucocorticoid receptors
- aldosterone receptors
Examples of receptors in the nucleus
- thyroid hormone receptor
- vit. D3 receptor
Specificity of Signaling
- cell must contain receptor
- specific set of gene regulatory proteins must be present in order to activate transciprtion
- some gene regulatory proteins are cell specific
Is signaling via intracellular receptors fast or slow? Why?
Slow = approx. 10 minutes at the fastest
Why?
- Long diffusion paths for ligand. Carrier proteins present a reservoir for ligands (=signal molecules)
- Effect requires transcription and translation
- Termination requires excretion of hormone (often as bile after conjugation in the liver)
Mineralocorticoid Receptor
Hormone: Aldosterone
Produced in response to decrease in blood pressure
Origin: Adrenal Cortex
-produced on demand - no storage!
Carrier protein: transcortin; albumin
ReceptorL Mineralocorticoid receptor
Effect:
-In Kidney: Na+ and H2O retention (and K+ excretion) leading to increase in blood pressure
What is renin?
An enzyme released by the kidney that helps lead to increase in blood pressure as a response to a drop in blood pressure
Why are ligands bound to carrier proteins in the blood stream?
Prevents excretion in the kidney
How long can ligands remain in the blood stream until they are excreted?
Hours (a relatively long time)
Thyroid Hormone Receptor
Hormone: Tri-iodo-thyronie (T3)
Released in response to cold and stress
Origin: Thyroid gland synthesizes and stores prohormone thyroxine (T4) from which one iodine is removed to generate T3
Carrier protein: Thyroxine-binding prealbumin, thyroxine-binding globulin
Receptor: thyroid hormone receptor
Effect:
- general increase in metabolism
- increased O2 consumption and ventilation
- thermogenesis
- mobilization of fat and protein
How does prohormone thyroxine, T4, play into the production of T3?
T4 is produced and stored in the thyroid gland. One iodine is removed from T4 iin the kidney/liver to make T3
TRH
thyrotropin releasing hormone
released by hypothalamus
TSH
thyroid stimulating hormone = thyrotropin
released by pituitary
Feline Hyperthyroidism
Presentation:
- weight loss, despite a good appetite
- rapid heat rate
- hyperexcitability
- vomiting/diarrhea
- poor hair coat
Diagnosis;
- rule out other diseases
- determination of plasma levels of T4
Prevalence:
-most common endocrine disorder in older cats
Suspected causes:
- cats living longer
- exposure to chemicels -> polybrominated diphenyl ethers (PBDEs- flame retardants)
Etiology of Feline Hyperthyroidism
- most often caused by a thyroid adenoma
- only 2% of affected cats are diagnosed with thyroid adenocarcinoma
- one or both lobes of thyroid gland may be involved
Treatment of Feline Hyperthyroidism
- Methimazole (Tapazol) - inhibits T3/T4 production
- Surgical removal of thyroid gland
- Radio-iodine treatment with Iodine 131 (iodine 127 is the stable, non-radioactive isotope)
Cats treated for feline hyperthyroidism with radio-iodine treatment need to remain in the hospital for 10-14 days post-treatment. Why?
- Iodine 131 has a half-life of 8 days
- Litter boxes are radioactive
Phosphorylation
conformation change of proteins
Which three amino acids contain -OH groups that are suitable for adding a phosphate group?
- Serine
- Threonine
- Tyrosine
kinase
adds a phosphate group
“phosphorylation”
phosphatase
takes a phosphate group off
“dephosphorylation”
Serine/Threonine kinases
- Protein Kinase A = A-kinase
- Protein Kinase C = C-kinase
- Protein Kinase G = G-kinase
- Calmodulin-Activated Kinase = CaM Kinase
- Mitogen-Activated Protein Kinase = MAP-kinase
Phosphatases involved in Phosphorylation
- Serine/Threonine Phopsphatases
- Tyrosine Phosphatase
Tysosine kinases
ex - insulin receptor
- many growth factors
- SRC
- JAK
